Inheritance can influence an individual's susceptibility to the damaging effects of his environment. Diseases arising from genetic- environmental interaction can be prevented if the inherited abnormality is detected prior to the injury and the environmental exposure avoided or modified. Alpha 1- antitrypsin deficiency (AATD) appears to predispose to chronic obstructive lung disease (COLD) through this mechanism. Other inherited predisposing factors will be uncovered. This project seeks to improve the methods for detecting AATD and clarify the mechanisms leading to lung damage in AATD so that preventive medicine programs can be planned. We will search for other inherited abnormalities which can influence susceptibility to lung disease. The role of immunoglobulin defects will be evaluated. Case finding surveys and prospective studies of patients and presumably healthy subjects will be employed to clarify the clinical, pathological, physiological and biochemical defects in these states. Family studies will be performed to determine inheritance patterns. We will assess the value of genetic information as an adjunct to smoking prevention counseling of junior high school students.